Genetic analysis of polygenic, quantitative traits remains an important challenge. It requires reliable scoring of many genetic markers covering the whole genome. In yeast, the first successful approaches to simultaneously map multiple genetic loci, that were either independent (Winzeler et al., 1998) or involved in a quantitative trait (QTL) Steinmetz et al., 2002), made use of SNP markers that were scored by hybridization of genomic DNA from individual segregants to a gene expression micro-array. Subsequently, a similar approach was used to map QTL involved in traits such as sporulation efficiency (Deutschbauer and Davies, 2005), gene expression (Brem et al., 2002), acetic acid production (Marullo et al., 2007), cell morphology (Nogami et al., 2007) and resistance to small-molecule drugs (Perlstein et al., 2007).
The advent of high-throughput sequencing technologies provides a new way to score large numbers of SNPs as genetic markers. Application to individual segregants remains cumbersome because of the high costs involved. On the other hand, bulked segregant analysis was shown to be efficient in identifying markers linked to specific genes (Michelmore et al., 1991) and is robust to occasional phenotyping mistakes (Segré et al., 2006). Schneeberger et al., (2009) showed that this approach worked for a single mutation. They crossed an Arabidopsis thaliana mutant with an unrelated strain, pooled 500 segregants with the mutant phenotype and used the nucleotide frequency of SNPs detected by Illumina whole genome sequence analysis in the DNA extracted from the pool to map the locus with the mutation. Recently, Arnold et al., (2011) used a similar approach to identify a single mutation responsible for a renal disease in mice and Birkeland et al., (2010) to map a mutation causing a defect in vacuole inheritance in S. cerevisiae. It has been suggested that in principle this approach should also allow the simultaneous mapping of multiple QTL present throughout the genome (Schneeberger et al., 2009; Birkeland et al., 2010; Lister et al., 2009). However, to the best of our knowledge, this has not been demonstrated yet for a typical quantitative trait.